Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial

Abstract

Background People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. Methods In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18–65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. Findings Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9–298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7–204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. ...

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…The vast majority of included studies evaluated vaccines developed by Pfizer (BNT162b2) or Moderna (mRNA-1273). Thirteen studies included patients who received the vaccine developed by Janssen (Ad26.COV2.S) [ [25] , [26] , [27] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] ], nine included patients vaccinated with the AstraZeneca vaccine (ChAdOx1) [ [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] ], three included patients receiving the CoronaVac vaccine (Sinovac Biotech) [ [50] , [51] , [52] ], and one randomized controlled trial evaluated the vaccine developed by Novavax (NVX-CoV2373) vaccine [ 53 ]. One study included patients receiving the BBV152-Covaxin (Bharat Biotech) vaccine [ 44 ] and one included patients receiving the BBIBP-CorV (Sinopharm) vaccine [ 54 ].…”

“…Most studies assessed anti-SARS-CoV-2 immunity through an immunoassay to detect antibodies targeted at the spike protein, including some targeting specifically the receptor-binding domain (RBD) of the spike protein. Thirty studies reported neutralization assay results in addition to anti-SARS-CoV-2 antibody assays [ 34 , 37 , 41 , 48 , 51 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] ]. Thirty-one studies provided data on cellular immunity [ 17 , 21 , 22 , 34 , 37 , 41 , 45 , 46 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 72 , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] , [84] ].…”

“…Five studies conducted in people living with HIV found low non-response rates ranging from 0 to 4% [ 48 , 68 , 179 ] (among those, two studies were estimated of good quality in the risk of bias assessment [ 48 , 68 ]) or comparable antibody titres compared to an HIV-negative population [ 41 , 67 ].…”

Prevention and Treatment of SARS-CoV2 Infection in People Living with HIV: The Need for Specific Data

“…Compared to HIV-uninfected persons of the same age, there were no differences in humoral and cell-mediated immune response after 56 days of follow-up [ 28 ]. An interim analysis of the COV005 trial in South Africa for the same vaccine showed that two doses were well tolerated with similar neutralizing response patterns in PLWH and HIV-negative participants [ 29 ]. A prospective study of the BNT162b2 (Pfizer) vaccine conducted in 143 virologically suppressed PLWH with high CD4 T-cell count found that 97% developed anti-RBD-IgG in this group, while 98.9% did in the control group.…”

Posicionamento da ASBAI sobre dose adicional e intercambialidade de vacinas contra a COVID-19

“…cepas variantes e menor distanciamento social e uso de medidas protetoras 7,8 . Observou-se uma redução da eficácia das vacinas de mRNA (Pfizer e Moderna) em relação à prevenção de infecções sintomáticas pelo coronavírus de cerca de 95% para 65% em trabalhadores da área da saúde 8 .…”